One goal of recombinant protein production is the optimization of culture conditions so as to obtain the greatest possible productivity. Even incremental increases in productivity can be economically significant.
CHO (Chinese hamster ovary) cell lines are often used for recombinant protein production because they grow well in either adherent or suspension culture, and efficiently produce many proteins. Further, CHO cells and recombinant proteins expressed in them have been extensively characterized and have been approved for use in clinical manufacturing by regulatory agencies.
Some of the methods to increase productivity in CHO cell culture include using enriched medium, monitoring and altering osmolarity during production, decreasing temperatures during specific phases of a cell culture, and/or the addition of sodium butyrate to induce expression during the production phase (see, for example, U.S. Pat. No. 5,705,364 to Etcheverry et al.). In addition, when CHO cells are grown in batch culture, periodic feeding of the cells with essential nutrients will also increase production (see, for example, U.S. Pat. No. 5,672,502 to Birch et al.).
However, there remains a need in the art to continually improve yields of recombinant protein from each cell culture run.